Lung CD11c+ cells from mice deficient in Epstein-Barr virus-induced gene 3 (EBI-3) prevent airway hyper-responsiveness in experimental asthma

Epstein-Barr virus-induced gene (EBI)-3 codes for a soluble type 1 cytokine receptor homologous to the p40 subunit of IL-12 that is expressed by antigen-presenting cells following activation. Here, we analyzed the functional role of EBI-3 in a murine model of asthma associated with airway hyper-responsiveness (AHR) in ovalbumin-sensitized mice. Upon allergen challenge, EBI-3(-/-) mice showed less severe AHR, decreased numbers and degranulation of eosinophils and a significantly reduced number of VCAM-1(+) cells in the lungs as compared to wild-type littermates. We thus analyzed lung CD11c(+) cells before and after allergen challenge in these mice and found that before allergen challenge, lung CD11c(+) cells isolated from EBI-3(-/-) mice express markers of a more plasmacytoid phenotype without releasing IFN-alpha as compared to those from wildtype littermates. Moreover, allergen challenge induced the development of myeloid CD11c(+) cells in the lungs of EBI-3(-/-) mice, which released increased amounts of IL-10 and IL-12 while not expressing IFN-alpha. Finally, inhibition of EBI-3 expression in lung DC could prevent AHR in adoptive transfer studies by suppressing mediator release of effector cells into the airways. These results indicate a novel role for EBI-3 in controlling local immune responses in-the lungs in experimental asthma.